Haworth worked out the correct structure of a number of sugars, and is known among organic chemists for his development of the Haworth projection that translates three-dimensional sugar structures into convenient two-dimensional graphical form.

He was appointed Professor of Organic Chemistry at the Armstrong College (Newcastle upon Tyne) of Durham University in 1920. The next year Haworth was appointed Head of the Chemistry Department at the college. It was during his time in the North East of England that he married Violet Chilton Dobbie.

In 1925 he was appointed Mason Professor of Chemistry at the University of Birmingham (a position he held until 1948). Among his lasting contributions to science was the confirmation of a number of structures of optically active sugars: by 1928, he had deduced and confirmed, among others, the structures of maltose, cellobiose, lactose, gentiobiose, melibiose, gentianose, raffinose, as well as the glucoside ring tautomeric structure of aldose sugars.

In 1933, working with the then Assistant Director of Research (later Sir) Edmund Hirst and a team led by post-doctoral student Maurice Stacey (who in 1956 rose to the same Mason Chair), having properly deduced the correct structure and optical-isomeric nature of vitamin C, Haworth reported the synthesisis of the vitamin.[6] Haworth had been given his initial reference sample of "water-soluble vitamin C" or "hexuronic acid" (the previous name for the compound as extracted from natural products) by Hungarian physiologist Albert Szent-György, who had codiscovered its vitamin properties along with Charles Glen King, and had more recently discovered that it could be extracted in bulk from Hungarian paprika. In honor of the compound's antiscorbutic properties, Haworth and Szent-Györgyi now proposed the new name of "a-scorbic acid" for the molecule, with L-ascorbic acid as its formal chemical name.

In 1977 the Royal Mail issued a postage stamp (one of a series of four) featuring Haworth's achievement in synthesizing vitamin C and his Nobel prize.[8]

He also developed a simple method of representing on paper the three-dimensional structure of sugars. The representation, using perspective, now known as a Haworth projection, is still widely used in biochemistry.[9]